Engineered extracellular matrices: Emerging strategies for decoupling structural and molecular signals that regulate epithelial branching morphogenesis

The extracellular matrix (ECM) is a heterogeneous mixture of proteoglycans and fibrous proteins that form the noncellular component of tissues and organs. During normal development, homeostasis, and disease progression, the ECM provides dynamic structural and molecular signals that influence the form and function of individual cells and multicellular tissues. Here, we review recent developments in the design and fabrication of engineered ECMs and the application of these systems to study the morphogenesis of epithelial tissues. We emphasize emerging techniques for reproducing the structural and molecular complexity of the native ECM, and we highlight how these techniques may be used to decouple the different signals that drive epithelial morphogenesis. Engineered models of the native ECM will enable further investigation of the dynamic mechanisms by which the microenvironment influences tissue morphogenesis.